PROJECT SUMMARY ? CORE C Core C, which supports every project within the Program, provides access to sophisticated imaging technologies and histopathology services, enabling Program investigators to use imaging to obtain insights into molecular and cellular mechanisms and to track tumor progression, therapy response, and metastasis. Imaging in cells and animals ? from the molecular, to tissue, to whole-body level ? is supported by the Core. Core C will assist with sub-cellular to whole-tissue level analysis of fixed cells and tissues, providing histopathological services through a subcontract with a world-class pathologist. The Core also supports live cell imaging in three and four dimensions (3D and 4D, also known as 3D time-lapse), and imaging in live animals. The imaging approaches offered by Core C include several cutting-edge imaging technologies, each of which is available in a limited number of locations worldwide. These include i) super-resolution (100 nm), and high-speed cellular imaging achieved with an OMX (Optical Microscope eXperimental) microscope; ii) 3D whole-tissue reconstruction of tumors and metastases using light-sheet microscopy; and iii) intravital (live animal) imaging using custom-built spinning disk confocal and multi-photon microscopes. During the upcoming period of requested support, Core C proposes to support Program investigators through four aims. First, the program will provide assistance with histology, immune labeling, and histopathology. Second, the Core will support live cell imaging and super-resolution imaging. Third, the Core will assist with imaging at the tissue level, either using 3D tissue reconstruction or live imaging in animals. These technologies each require custom-built microscopes that are not generally available. Fourth, to provide Program investigators with tools to track tumor growth and metastasis, Core C will assist with whole animal imaging approaches, including bioluminescence, fluorescent proteins, and small animal ultrasound. Core C will also assist with the use of advanced imaging software, including Image J (NIH), Imaris (Bitplane), and Volocity (Perkin-Elmer). New in this renewal is support for quantification of micrometastasis, intravital imaging through surgically implanted windows, and 3D tissue reconstruction using light-sheet microscopy. Together, Core C has an unprecedented imaging platform, covering super-resolution imaging, 3D tissue reconstruction, live cell tracking in tissues and whole animal imaging. A Core that enables program investigators access to these technologies is essential as most of the imaging technologies supported by the Core are highly sophisticated and require very specialized training. Furthermore, access to the instruments required for these imaging technologies would be cost-prohibitive without the support of a Core. Thus, Core C will provide critical tools for Program members and, through the development of new imaging approaches, ultimately the broader cancer research community.